IDE196 Combinations for Solid Tumors
Recruiting in Palo Alto (17 mi)
+9 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: IDEAYA Biosciences
Must not be taking: Statins, ALK inhibitors
Disqualifiers: Symptomatic brain metastases, AIDS, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.
Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study.
Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity.
As of Protocol Amendment 10, Phase 1, Phase 2 dose expansion in IDE196 monotherapy, and Phase 2 dose expansion of IDE196 in combination with binimetinib have been fully enrolled. There were no patients enrolled in the crizotinib monotherapy cohorts.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it mentions that treatment with prohibited medications that cannot be discontinued prior to study entry is an exclusion criterion. It would be best to discuss your current medications with the trial team to determine if any need to be stopped.
What makes the drug IDE196 unique for treating solid tumors?
IDE196 (Darovasertib) is unique because it targets a specific protein involved in cancer cell growth, making it potentially effective for tumors with certain genetic mutations. This targeted approach is different from traditional chemotherapy, which affects all rapidly dividing cells.
12345Eligibility Criteria
This trial is for adults with certain solid tumors, including metastatic uveal melanoma, skin cancer, and colorectal cancer that have specific genetic mutations or fusions. Participants must have had prior treatment with a MEK inhibitor (except for Binimetinib Combination), measurable disease, good performance status (ECOG ≤1), life expectancy over 3 months, adequate organ function and cardiac function (for Binimetinib Combination), and agree to use contraception. Exclusions include symptomatic brain metastases, pregnancy/breastfeeding women, recent thromboembolic events or surgeries.Inclusion Criteria
I am 18 years old or older.
I have a history of fainting.
My organs are working well.
+11 more
Exclusion Criteria
I have previously been treated with a MEK inhibitor.
I have a muscle disorder that increases my CPK levels.
I have a history of fainting.
+21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase 1 Dose Escalation
Assessment of safety, tolerability, and pharmacokinetics of IDE196, alone and in combination with binimetinib or crizotinib, to determine the recommended Phase 2 dose
28 days per cycle
Phase 2 Dose Expansion
Evaluation of safety and anti-tumor activity of IDE196, alone and in combination with binimetinib or crizotinib, at the recommended Phase 2 dose
Approx. 6 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Approx. 48 months
Participant Groups
The study tests the safety and effectiveness of IDE196 alone or in combination with Crizotinib or Binimetinib in patients whose tumors have GNAQ/11 mutations or PRKC fusions. It includes dose escalation to find the right amount of drug and then expands to more patients at this dose. The effects of food on IDE196's absorption are also studied.
9Treatment groups
Experimental Treatment
Group I: PK Substudy with Pravastatin (OBTP1B1 Substrate)Experimental Treatment1 Intervention
A PK substudy with approximately 18 patients will be nested within the IDE196 and crizotinib combination expansion cohort to evaluate the impact on the pravastatin PK profile by the steady state exposures of IDE196.
Group II: Dose Optimization Crizotinib CombinationExperimental Treatment2 Interventions
IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
Group III: Dose Expansion MonotherapyExperimental Treatment1 Intervention
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)
Group IV: Dose Expansion Crizotinib CombinationExperimental Treatment2 Interventions
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) Previously treated MUM, Treatment naïve MUM, MUM patients with human leukocyte antigen (HLA)-A\*02:01 positive status
Group V: Dose Expansion Binimetinib CombinationExperimental Treatment2 Interventions
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
Group VI: Dose Escalation MonotherapyExperimental Treatment1 Intervention
IDE196 dosed orally, twice daily (BID) for each 28-day cycle
Group VII: Dose Escalation Crizotinib CombinationExperimental Treatment2 Interventions
IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
Group VIII: Dose Escalation Binimetinib CombinationExperimental Treatment2 Interventions
IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle
Group IX: Crizotinib Monotherapy with Crossover to CombinationExperimental Treatment2 Interventions
Crizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Cincinnati Cancer CenterCincinnati, OH
The Sarah Cannon Research Institute/Tennessee OncologyNashville, TN
Sidney Kimmel Cancer Center at Thomas Jefferson UniversityPhiladelphia, PA
Princess Margaret Cancer CentreToronto, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
IDEAYA BiosciencesLead Sponsor
References
A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515). [2022]Prexasertib (LY2606368) is a novel, second-generation, selective dual inhibitor of checkpoint kinase proteins 1 (CHK1) and 2 (CHK2). We conducted a phase 1 trial of prexasertib to estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), to define and describe the toxicities, and to characterize the pharmacokinetics (PK) of prexasertib in pediatric patients with recurrent or refractory solid and central nervous system (CNS) tumors.
Phase I/II study of the WEE1 inhibitor adavosertib (AZD1775) in combination with carboplatin in children with advanced malignancies: Arm C of the AcSé-ESMART trial. [2023]AcSé-ESMART Arm C aimed to define the recommended dose and activity of the WEE1 inhibitor adavosertib in combination with carboplatin in children and young adults with molecularly enriched recurrent/refractory malignancies.
Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID). [2022]Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel.
Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models. [2022]CRM1 inhibitors have demonstrated antitumor effects in ovarian and other cancers; however, rational combinations are largely unexplored. We performed a high-throughput drug library screen to identify drugs that might combine well with selinexor in ovarian cancer. Next, we tested the combination of selinexor with the top hit from the drug screen in vitro and in vivo Finally, we assessed for mechanisms underlying the identified synergy using reverse phase protein arrays (RPPA). The drug library screen assessing 688 drugs identified olaparib (a PARP inhibitor) as the most synergistic combination with selinexor. Synergy was further demonstrated by MTT assays. In the A2780luc ip1 mouse model, the combination of selinexor and olaparib yielded significantly lower tumor weight and fewer tumor nodules compared with the control group (P < 0.04 and P < 0.03). In the OVCAR5 mouse model, the combination yielded significantly fewer nodules (P = 0.006) and markedly lower tumor weight compared with the control group (P = 0.059). RPPA analysis indicated decreased expression of DNA damage repair proteins and increased expression of tumor suppressor proteins in the combination treatment group. Collectively, our preclinical findings indicate that combination with selinexor to expand the utility and efficacy of PARP inhibitors in ovarian cancer warrants further exploration.
SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. [2023]Integrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple investigators to be a negative prognostic indicator in diverse cancers including colorectal, non-small cell lung, gastric, and cervical. We developed SGN-B6A as an antibody-drug conjugate (ADC) directed to integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE) to cancer cells. The antibody component of SGN-B6A is specific for integrin beta-6 and does not bind other alpha-v family members. In preclinical studies, this ADC has demonstrated activity in vivo in models derived from non-small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. In nonclinical toxicology studies in cynomolgus monkeys, doses of up to 5 mg/kg weekly for four doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed. A phase I first-in-human study is in progress to evaluate the safety and antitumor activity of SGN-B6A in a variety of solid tumors known to express integrin beta-6 (NCT04389632).